Ionizing radiation induces mutations. This has been regarded as the prime genetic hazard to human populations from the increased and increasing presence of ionizing radiation in modern society. It is possible that a far greater genetic hazard from radiation would be induction of mutants that enhance the spontaneous mutation rate (mutator mutants). Thus mutations could accumulate every generation, even after exposure to the radiation had ceased. We have devised a sensitive method for measuring the spontaneous mutation rate in the yeast Saccharomyces cerevisiae. It is essentially a 1000-compartment fluctuation test. Upon screening for mutator mutants after mutagenizing with ethyl methanesulfonate, we found over 100 mutator mutants in the first experiment. This finding, and the common occurrence of mutator strains among controls, indicates that mutations which cause mutation enhancement are easily inducible and recognizable. We propose to study the kinetics of induction of mutants in yeast which confer mutator or antimutator activity. Thus it would be possible to estimate characteristics of the spontaneous mutation rate which stabilize it, and to determine whether these stabilizing influences hold constant after exposure to increasing doses of ionizing radiation. From these data we expect to be able to make a rough approximation of this type of genetic hazard from irradiation of human populations. BIBLIOGRAPHIC REFERENCES: Drake, J.W., S. Abrahamson, J.F. Crow, A. Hollaender, S. Lederberg, M.S. Legator, J.V. Neel, M.W. Shaw, H.E. Sutton, R.C. von Borstel and S. Zimmering, 1975, Environmental mutagenic hazards. Science 187:503-514. Plischke, M.E., R.C. von Borstel, R.K. Mortimer and W.E. Cohn, 1976, Genetic markers and associated gene products in Saccharomyces cerevisiae. In Handbook of Biochemistry and Molecular Biology, third edition, Nucleic Acids -- Volume II, (G.D. Fasman, ed.), pp. 767-832, Chemical Rubber Company Press, Cleveland.